Vascular tenascin-C regulates cardiac endothelial phenotype and neovascularization

被引:66
作者
Ballard, Victoria L. T.
Sharma, Arti
Duignan, Inga
Holm, Jacquelyne M.
Chin, Andrew
Choi, Ruby
Hajjar, Katherine A.
Wong, Shing-Chiu
Edelberg, Jay M.
机构
[1] Cornell Univ, Weill Med Coll, Dept Med, Div Cardiol, New York, NY 10021 USA
[2] Cornell Univ, Weill Med Coll, Dept Cell & Dev Biol, New York, NY 10021 USA
关键词
heart; bone marrow; angiogenesis; EPC;
D O I
10.1096/fj.05-5131fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Microenvironmental cues mediate postnatal neovascularization via modulation of endothelial cell and bone marrow-derived endothelial progenitor cell (EPC) activity. Numerous signals regulate the activity of both of these cell types in response to vascular injury, which suggests that parallel mechanisms regulate angiogenesis in the vascular beds of both the heart and bone marrow. To identify mediators of such shared pathways, in vivo bone marrow/cardiac phage display biopanning was performed and led to the identification of tenascin-C as a candidate protein. Functionally, tenascin-C inhibits cardiac endothelial cell spreading and enhances migration in response to angiogenic growth factors. Analysis of human coronary thrombi revealed tenascin-C protein expression colocalized with the endothelial cell/EPC marker Tie-2 in intrathrombi vascular channels. Immunostains in the rodent heart demonstrated that tenascin-C also colocalizes with EPCs homing to sites of cardiac angiogenic induction. To determine the importance of tenascin-C in cardiac neovascularization, we used an established cardiac transplantation model and showed that unlike wild-type mice, tenascin-C-/- mice fail to vascularize cardiac allografts. This demonstrates for the first time that tenascin-C is essential for postnatal cardiac angiogenic function. Together, our data highlight the role of tenascin-C as a microenvironmental regulator of cardiac endothelial/EPC activity.
引用
收藏
页码:717 / +
页数:22
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